IMPORTANCE A major challenge for drug development in neurodegenerative diseases is that adequately powered efficacy studies with meaningful end points typically require several hundred participants and long durations. Prion diseases represent the archetype of brain diseases caused by protein misfolding, the most common subtype being sporadic Creutzfeldt-Jakob disease (sCJD), a rapidly progressive dementia. There is no well-established trial method in prion disease. OBJECTIVE To establish a more powerful and meaningful clinical trial method in sCJD. DESIGN, SETTING, AND PARTICIPANTS A stratified medicine and simulation approach based on a prospective interval-cohort study conducted from October 2008 to June 2014. This study involved 598 participants with probable or definite sCJD followed up over 470 patient-years at a specialist national referral service in the United Kingdom with domiciliary, care home, and hospital patient visits. We fitted linear mixed models to the outcome measurements, and simulated clinical trials involving 10 to 120 patients (no dropouts) with early to moderately advanced prion disease using model parameters to compare the power of various designs. MAIN OUTCOMES AND MEASURES A total of 2681 assessments were done using a functionally orientated composite end point (Medical Research Council Scale) and associated with clinical investigations (brain magnetic resonance imaging, electroencephalography, and cerebrospinal fluid analysis) and molecular data (prion protein [PrP] gene sequencing, PrPSc type). RESULTS Of the 598 participants, 273 were men. The PrP gene sequence was significantly associated with decline relative to any other demographic or investigation factors. Patients with sCJD and polymorphic codon 129 genotypes MM, VV, and MV lost 10% of their function in 5.3 (95% CI, 4.2-6.9), 13.2 (95% CI, 10.9-16.6), and 27.8 (95% CI, 21.9-37.8) days, respectively (P < .001). Simulations indicate that an adequately powered (80%; 2-sided α = .05) open-label randomized trial using 50% reduction in Medical Research Council Scale decline as the primary outcome could be conducted with only 120 participants assessed every 10 days and only 90 participants assessed daily, providing considerably more power than using survival as the primary outcome. Restricting to VV or MV codon 129 genotypes increased power even further. Alternatively, single-arm intervention studies (half the total sample size) could provide similar power in comparison to the natural history cohort. CONCLUSIONS AND RELEVANCE Functional end points in neurodegeneration need not require long and very large clinical studies to be adequately powered for efficacy. Patients with sCJD may be an efficient and cost-effective group for testing disease-modifying therapeutics. Stratified medicine and natural history cohort approaches may transform the feasibility of clinical trials in orphan diseases.

Background:Delayed-release dimethyl fumarate (DMF), indicated for the treatment of patients with relapsing-remitting multiple sclerosis (MS), is a disease-modifying therapy with potential immunomodulatory and neuroprotective effects. In clinical trials, DMF was associated with reduced white blood cell and absolute lymphocyte counts. Current US prescribing information recommends obtaining a complete blood count, including absolute lymphocyte count (ALC), before initiating and during DMF treatment. Methods:We conducted an integrated analysis of phase 2b/3/long-term extension studies of DMF in MS (N = 2,470) to characterize ALC profiles. Results:Mean ALCs decreased by 30% during the first year and then plateaued, remaining above the lower limit of normal (LLN). Among patients treated ≥6 months (N = 2,099), 2.2% experienced ALCs <500 mm3 persisting ≥6 months. ALCs remained ≥LLN in 84% and 76% of patients during the first 6 and 12 months, respectively; of these, 0.1% and 0%, respectively, developed ALCs <500 mm3 persisting ≥6 months at any time. Evidence of ALC improvement following DMF discontinuation was observed. DMF efficacy was not substantially different in patients with and without lymphopenia. Conclusion:Lymphocyte monitoring provides effective means for early identification of patients at risk for developing severe, prolonged lymphopenia.

Aim: The aim of this study was to analyze frequency of restless legs syndrome (RLS) in patients with hypertension and diabetes mellitus. Patients and Methods: It was analyzed 120 subjects (from Health Center Živinice/Family Medicine Department) through a survey conducted in the period from March to June 2015, of which 30 (8 men/22 women). Subjects were 30 patients with longtime hypertension (HT)(18 men/12 women), 30 patients with diabetes mellitus (DM) type I or II (9 men/21 women), 30 patients with long standing DM type I or II and HT (12 men /18 women), and 30 control subjects (12 men/18 women). RLS were evaluated by questionnaire - International RLS Study Group Criteria. The average age of patients in the group with HT was 58.70 ± 9.07, in the group with DM 48.43 ± 15.37, and in the group of patients with HT and DM 63.90 ± 7.49 years. In the control group mean age was 52.76 ± 14.83 years. Statistical data were analyzed in Excel and SSPS statistical program. Results: RLS was identified in 10 (30%) of those with HT; 7 (21%) in patients with DM, and 10 (30%) in patients with HT+DM. In the control group RLS was verified in 4 (12%) patients. Comparing the results, it was observed significant difference between the HT and the control group (p=0.0012) and HT+ DM and control group (p=0.0012). The frequency of RLS between DM and the control group was not significantly significant (p=0.107). Conclusion: RLS is frequent in patients with hypertension (30%), hypertension+ diabetes mellitus (30%), and patients with DM (21%).

Table of contents OP03 Selective extraction of medically-related radionuclides from proton-irradiated thorium targets V. Radchenko, J.W. Engle, C. Roy, J. Griswold, M.F. Nortier, E.R. Birnbaum, M. Brugh, S. Mirzadeh, K. D. John, M.E. Fassbender OP04 Comparison of [68Ga]FSC(succ-RGD)3 and [68Ga]NODAGA-RGD for PET imaging of αvβ3 integrin expression Chuangyan Zhai, Gerben M. Franssen, Milos Petrik, Peter Laverman, Clemens Decristoforo OP05 A new NPY-Y1R targeting peptide for breast cancer PET imaging Ait-Mohand Samia, Dumulon-Perreault Véronique, Guérin Brigitte OP06 The influence of multivalency on CCK 2 receptor targeting D. Summer, A. Kroess, C. Rangger, H. Haas, P. Laverman, F. Gerben, E. von Guggenberg, C.Decristoforo OP07 SPECT Imaging of αvβ3 Expression by [99mTc(N)PNP43]- Bifunctional Chimeric RGD Peptide not Cross-Reacting with αvβ5 Cristina Bolzati, Nicola Salvarese, Fiorenzo Refosco, Laura Meléndez-Alafort, Debora Carpanese, Antonio Rosato, Michele Saviano, Annarita Del Gatto, Daniela Comegna, Laura Zaccaro OP09 New dienophiles for the inverse-electron-demand Diels-Alder reaction and for pretargeted PET imaging Emilie Billaud, Muneer Ahamed, Frederik Cleeren, Elnaz Shahbazali, Tim Noël, Volker Hessel, Alfons Verbruggen and Guy Bormans OP10 New complexing agent for Al18F-labelling of heat-sensitive biomolecules: Synthesis and preclinical evaluation of Al18F-RESCA1-HAS Cleeren F, Lecina J, Koole M, Verbruggen A and Bormans G OP11 A novel versatile precursor efficient for F-18 radiolabelling via click-chemistry B. Lugatoa, S. Stucchia, E.A. Turollaa, L. Giulianoa, S.Toddea, P. Ferraboschib OP12 A general applicable method to quantify unidentified UV impurities in radiopharmaceuticals R.P. Klok, M.P.J. Mooijer, N.H. Hendrikse, A.D. Windhorst OP13 Development of [18F]Fluoro-C-glycosides to radiolabel peptides Collet C., Petry N., Chrétien F., Karcher G., Pellegrini-Moïse N., Lamandé-Langle S. OP14 A Microfluidic Approach for the 68Ga-labeling of PSMAHBED-CC and NODAGA-RGD Sarah Pfaff, Cecile Philippe, Markus Mitterhauser, Marcus Hacker, Wolfgang Wadsak OP16 Surprising reactivity of astatine in the nucleophilic substitution of aryliodonium salts: application to the radiolabeling of antibodies François Guérard, Yong-Sok Lee, Sébastien Gouard, Kwamena Baidoo, Cyrille Alliot, Michel Chérel, Martin W. Brechbiel, Jean-François Gestin OP17 64Cu-NOTA-pertuzumab F(ab')2 fragments, a second-generation probe for PET imaging of the response of HER2-positive breast cancer to trastuzumab (Herceptin) Lam K, Chan C, Reilly RM OP18 Development of radiohalogenated analogues of a avb6-specific peptide for high LET particle emitter targeted radionuclide therapy of cancer Salomé Paillas, John Marshall, Jean-Pierre Pouget, Jane Sosabowski OP19 Ligand Specific Efficiency (LSE) as a guide in tracer optimization Emmanuelle Briard, Yves P. Auberson, John Reilly, Mark Healy, David Sykes OP23 The radiosynthesis of an 18F-labeled triglyceride, developed to visualize and quantify brown adipose tissue activity Andreas Paulus, Wouter van Marken Lichtenbelt,Felix Mottaghy, Matthias Bauwens OP24 Influence of the fluorescent dye on the tumor targeting properties of dual-labeled HBED-CC based PSMA inhibitors Baranski, Ann-Christin, Schäfer, Martin, Bauder-Wüst, Ulrike, Haberkorn, Uwe, Eder, Matthias, Kopka, Klaus OP25 [18F]MEL050 as a melanin PET tracer : fully automated radiosynthesis and evaluation for the detection of pigmented melanoma in mice pulmonary metastases Chaussard M, Hosten B, Vignal N, Tsoupko-Sitnikov V, Hernio N, Hontonnou F, Merlet P, Poyet JL, Sarda-Mantel L, Rizzo-Padoin N OP26 Design and Preclinical Evaluation of Novel Radiofluorinated PSMA Targeting Ligands Based on PSMA-617 J. Cardinale, M. Schäfer, M. Benešová, U. Bauder-Wüst, O. Seibert, F. Giesel, U. Haberkorn, M. Eder, K. Kopka OP27 A novel radiolabeled peptide for PET imaging of prostate cancer: 64Cu-DOTHA2-PEG-RM26 Mansour Nematallah, Paquette Michel, Ait-Mohand Samia, Dumulon-Perreault Véronique, Lecomte Roger, Guérin Brigitte OP29 Biodistribution of [18F]Amylovis®, a new radiotracer PET imaging of β-amyloid plaques Fernandez-Maza L, Rivera-Marrero S, Prats Capote A, Parrado-Gallego A, Fernandez-Gomez I, Balcerzyk M, Sablon-Carrazana M, Perera-Pintado A, Merceron-Martinez D, Acosta-Medina E, Rodriguez-Tanty C OP30 Synthesis and preclinical evaluation of [11C]-BA1 PET tracer for the imaging of CSF-1R Bala Attili, Muneer Ahamed, Guy Bormans OP31 In vivo imaging of the MCHR1 in the ventricular system via [18F]FE@SNAP C. Philippe, M. Zeilinger, T. Scherer, C. Fürnsinn, M. Dumanic, W. Wadsak, M. Hacker, M. Mitterhauser OP32 Synthesis of the first carbon-11 labelled P2Y12 receptor antagonist for imaging the anti-inflammatory phenotype of activated microglia B. Janssen, D.J. Vugts, G.T. Molenaar, U. Funke, P.S. Kruijer, F. Dollé, G. Bormans, A.A. Lammertsma, A.D. Windhorst OP33 Radiosynthesis of a selective HDAC6 inhibitor [11C]KB631 and in vitro and ex vivo evaluation Koen Vermeulen, Muneer Ahamed, Michael Schnekenburger, Mathy Froeyen, Dag Erlend Olberg, Marc Diederich, Guy Bormansa OP34 Improving metabolic stability of fluorine-18 labelled verapamil analogues Raaphorst RM, Luurtsema G, Lammertsma AA, Elsinga PH, Windhorst AD OP36 Development of a novel PET tracer for the activin receptor-like kinase 5 Lonneke Rotteveel, Uta Funke, Peter ten Dijke, Harm Jan Bogaard, Adriaan A. Lammertsma, Albert D. Windhorst OP37 SPECT imaging and biodistribution studies of 111In-EGF-Au-PEG nanoparticles in vivo Lei Song, Sarah Able, Nadia Falzone, Veerle Kersemans, Katherine Vallis OP38 Melanoma targeting with [99mTc(N)(PNP3)]-labeled NAPamide derivatives: preliminary pharmacological studies Davide Carta, Nicola Salvarese, Wiebke Sihver, Feng Gao, Hans Jürgen Pietzsch, Barbara Biondi, Paolo Ruzza, Fiorenzo Refosco, Cristina Bolzati OP39 [68Ga]NODAGA-RGD: cGMP synthesis and data from a phase I clinical study Roland Haubner, Armin Finkensted, Armin Stegmair, Christine Rangger, Clemens Decristoforo, Heinz Zoller, Irene J. Virgolin OP44 Implementation of a GMP-grade radiopharmacy facility in Maastricht Ivo Pooters, Maartje Lotz, Roel Wierts, Felix Mottaghy, Matthias Bauwens OP45 Setting up a GMP production of a new radiopharmaceutical Forsback, Sarita, Bergman Jörgen, Kivelä Riikka OP48 In vitro and in vivo evaluation of 68-gallium labeled Fe3O4-DPD nanoparticles as potential PET/MRI imaging agents M. Karageorgou, M. Radović, C. Tsoukalas, B. Antic, M. Gazouli, M. Paravatou-Petsotas, S. Xanthopouls, M. Calamiotou, D. Stamopoulos, S. Vranješ-Durić, P. Bouziotis OP49 Fast PET imaging of inflammation using 68Ga-citrate with Fe-containing salts of hydroxy acids A. S. Lunev, A. A. Larenkov, K.A. Petrosova, O. E. Klementyeva, G. E. Kodina PP01 Installation and validation of 11C-methionine synthesis Kvernenes, O.H., Adamsen, T.C.H. PP02 Fully automated synthesis of 68Ga-labelled peptides using the IBA Synthera® and Synthera® Extension modules René Martin, Sebastian Weidlich, Anna-Maria Zerges, Cristiana Gameiro, Neva Lazarova, Marco Müllera PP03 GMP compliant production of 15O-labeled water using IBA 18 MeV proton cyclotron Gert Luurtsema, Michèl de Vries, Michel Ghyoot, Gina van der Woude, Rolf Zijlma, Rudi Dierckx, Hendrikus H. Boersma, Philip H. Elsinga PP04 In vitro Nuclear Imaging Potential of New Subphthalocyanine and Zinc Phthalocyanine Fatma Yurt Lambrecht, Ozge Er, Mine Ince, Cıgır Biray Avci, Cumhur Gunduz, Fatma Aslihan Sarı PP05 Synthesis, Photodynamic Therapy Efficacy and Nuclear Imaging Potential of Zinc Phthalocyanines Kasim Ocakoglu, Ozge Er, Onur Alp Ersoz, Fatma Yurt Lambrecht, Mine Ince, Cagla Kayabasi, Cumhur Gunduz PP06 Radio-U(H)PLC – the Search on the Optimal Flow Cell for the γ-Detector Torsten Kniess, Sebastian Meister, Steffen Fischer, Jörg Steinbach PP07 Radiolabeling, characterization & biodistribution study of cysteine and its derivatives with Tc99m Rabia Ashfaq, Saeed Iqbal, Atiq-ur-Rehman, Irfan ullah Khan PP08 Radiolabelling of poly (lactic-co.glycolic acid) (PLGA) nanoparticles with 99mTC R Iglesias-Jerez, Cayero-Otero, L. Martín-Banderas, A. Perera-Pintado, I. Borrego-Dorado PP09 Development of [18F]PD-410 as a non-peptidic PET radiotracer for gastrin releasing peptide receptors Ines Farinha-Antunes, Chantal Kwizera, Enza Lacivita, Ermelinda Lucente, Mauro Niso, Paola De Giorgio, Roberto Perrone, Nicola A. Colabufo, Philip H. Elsinga, Marcello Leopoldo PP10 An improved nucleophilic synthesis of 2-(3,4-dimethoxyphenyl)-6-(2-[18F]fluoroethoxy) benzothiazole ([18F]FEDMBT), potential diagnostic agent for breast cancer imaging by PET V.V. Vaulina, O.S. Fedorova, V.V. Orlovskaja, С.L. Chen, G.Y. Li, F.C. Meng, R.S. Liu, H.E. Wang, R.N. Krasikova PP11 Internal radiation dose assessment of radiopharmaceuticals prepared with accelerator-produced 99mTc Laura Meléndez-Alafort, Mohamed Abozeid, Guillermina Ferro-Flores, Anna Negri, Michele Bello, Nikolay Uzunov, Martha Paiusco, Juan Esposito, Antonio Rosato PP12 A specialized five-compartmental model software for pharmacokinetic parameters calculation Laura Meléndez-Alafort, Cristina Bolzati, Guillermina Ferro-Flores, Nicola Salvarese, Debora Carpanese, Mohamed Abozeid, Antonio Rosato, Nikolay Uzunov PP13 Molecular imaging of the pharmacokinetic behavior of low molecular weight 18F-labeled PEtOx in comparison to 89Zr-labeled PEtOx Palmieri L, Verbrugghen T, Glassner M, Hoogenboom R, Staelens S, Wyffels L PP14 Towards nucleophilic synthesis of the α-[18F]fluoropropyl-L-dihydroxyphenylalanine V. V. Orlovskaja, O. F. Kuznetsova, O. S. Fedorova, V. I. Maleev, Yu. N. Belokon, A. Geolchanyan, A. S. Saghyan, L. Mu, R. Schibli, S. M. Ametamey, R. N. Krasikova PP15 A convenient one-pot synthesis of [18F]clofarabine Revunov, Evgeny, Malmquist, Jonas, Johnström, Peter, Van Valkenburgh, Juno, Steele, Dalton, Halldin, Christer, Schou, Magnus PP16 BODIPY-estradiol conjugates as multi-modality tumor imaging agents Samira Osati,Michel P

Aim: The study deals with the effects of new system of rehabilitation by using individual dynamic programs through computer technology in the education and rehabilitation of persons with hearing impairments. The sample includes adolescents of both gender distribution with the hearing impairment, average intellectual abilities, between 15 and18 years of calendar age, attending the secondary vocational training school (N=49). Results: The results point to a significant statistical difference between the achievements of the examinees who underwent the classical educational rehabilitation treatment and those whose education was based on individual dynamic programs through computer technology, in favor of the latter. Conclusion: The study deals up with new social, cultural and science perspectives viewed throw the implementation of assistive technology in education and rehabilitation of deaf people.

Introduction: Renin-angiotenzin system (RAS) is frequently activated in patients with chronic liver disease. Angiotenzin - II (AT-II), produced by angiotenzin converting enzyme (ACE), has many physiological effects, including an important role in liver fibrogenesis. Combined antiviral therapy with PEG-IFN and ribavirin besides its antiviral effect also leads to a reduction in liver parenchyma fibrosis. Aim of the study: Determining the value of ACE in serum of patients with chronic hepatitis C before and after combined antiviral therapy, as well as the value of ACE activities in sera of the control group. Materials and methods: We studied 50 patients treated at Gastroenterohepatology Department, in the time-period of four years. Value of ACE in serum was determined by Olympus AU 400 device, with application of kit “Infinity TN ACE Liquid Stable Reagent”. HCV RNA levels in sera were measured by real time PCR. HCV RNA test was performed with modular analysis of AMPLICOR and COBAS AMPLICOR HCV MONITOR test v2.0, which has proved infection and was used for quantification of the viruses and monitoring of the patients’ response to therapy. Liver histology was evaluated in accordance with the level of necroinflammation activity and stage of fibrosis. Results: Serum activities of ACE in chronic hepatitis C patients is statistically higher than the values in the control group (p=0.02). Antiviral therapy in chronic hepatitis C patients statistically decreases serum activities of ACE (p= 0.02) and indirectly affects fibrogenesis of the liver parenchyma. Correlation between ACE and ALT activity after the therapy was proved (0.3934). Conclusion: Our findings suggest that the activity of ACE in serum is a good indirect parameter of the liver damage, and could be used as an indirect prognostic factor of the level of liver parenchyma damage. Serum activity of ACE can be used as a parameter for non-invasive assessment of intensity of liver damage.

Introduction: Faculty of Medicine, University of Sarajevo has officially started working on 22.11.1944, and is the oldest faculty in the medical field in Bosnia and Herzegovina. At the same time there are two systems of organization of the teaching process, the old system and the Bologna system. Aim: To analyze the implementation of the Bologna system, and making an overview of its justification. Material and methods: Answers from questionnaires from total of 459 students were analyzed (197 who had studied under the old system and 262 who studied under the Bologna system), so total of four generations of the Bologna system. They filled out a questionnaire in which they evaluated the teaching process. Student’s opinion about quality of medical education was measured by modified Lickert scale. Results: Students of old system are older than students of the Bologna process, whose average age is increasing from generation to generation, given the growing number of students who repeat a year. All students of old system repeated an academic year once or several times (p <0.05). Analysis of average grades showed statistically significant difference (p <0.05), where students in the Bologna system had higher averages than students who were studying under the old system. The presence of large number of female students, in both systems is significant (p <0.05). Out of 33 questions about satisfaction of class, 15 were answered with better average grade from students of the Bologna system. A slight improvement in the Bologna system is in terms of the evaluation of the quality of the educational process (teachers, methods, effects). The only significant progress has been proven in terms of rating the degree of computerization of the educational process–general records on enrolled students (old system vs Bologna system–3,44 vs 3,63), record of attendance (3,47 vs 3,73), obtaining certificates (3,08 vs 3,84), method of registration of exam (2,98 vs 3,71), method of practical exam (3,06 vs 3,36) and theoretical methods of taking exam (3,01 vs 3,14). Average grades where no average grade, on any issue, does not reach grade 4 of Likert Scale, talks about real problems of education in medical field. Conclusion: In a relatively large sample (four generations of students) true benefit and progress of the Bologna system has not been proven, in comparison to the old system. Bologna system has eased the students in the administrative sense by introduction of computerization of faculties, but the old problems and old questions about the organization’s process and delivery have not been eliminated.